The purpose of this proposal is to examine the activity of natural killer (NK) cells in the human lung. Natural killer cells are a morphologically distinct subpopulation of cells which have a variety of functions that may be pertinent to understanding cellular immune mechanisms in the lung which are directed against neoplastic disease. NK cells have been shown to: A) spontaneously kill tumor cells in vitro, B) limit the development of metastatic lesions in vivo, and C) interact with macrophages, dendritic cells and lymphocytes in ways that may regulate the development of cell mediated immunity. These observations suggest that NK cells may be important in tumor defense in the human lung. This hypothesis will be tested by purifying lymphocytes expressing NK markers from resected lung specimens. The effector, secretory and accessory cell function of pulmonary NK subsets will be studied directly. In addition, the location of pulmonary NK in the lung will be determined by immunohistological techniques. The role that pulmonary macrophages may play in regulating pulmonary NK, which may be important in vivo will also be determined. Information derived from these experiments should be valuable to understanding a possible mechanism of pulmonary defense against neoplastic disease.